Type 2 IP3 receptors are involved in uranyl acetate induced apoptosis in HEK 293 cells

Calcium released from endoplasmic reticulum through special calcium release channels – inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) – serves as a main source of cytosolic calcium signaling in the majority of cell types in physiological state and also in pathological situations. In this work, we studied whether IP3Rs can be involved in uranyl acetate induced nephrotoxicity. Using human embryonic kidney cell line (HEK293) as an experimental model we have found that uranyl acetate (5 and 50 μM) up-regulates both, mRNA and protein levels of the type 1 and type 2 IP3 receptors in HEK293 cells. This increase was associated with elevated expression of proapoptotic factors Bax and Caspase 3 and also by higher extent of apoptosis. Vice versa, induction of apoptosis resulted in increased mRNA levels of IP3R2 and also elevated levels of apoptotic markers. Therefore we propose that enhanced expression of the type 2 IP3Rs can at least partially contribute to increased levels of apoptosis due to uranyl acetate treatment.